Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy

Abstract

Background: Bacterial vaginosis (BV) is the single most common vaginal infection in women of childbearing age and associated with a sizeable infectious disease burden among both non-pregnant and pregnant women, including a significantly elevated risk of adverse pregnancy outcome. Overall, little progress has been made in identifying causal factors involved in BV acquisition and persistence. We sought to evaluate maternal iron status in early pregnancy as a putative risk factor for BV, considering that micronutrients, and iron deficiency in particular, affect the host response against bacterial colonization, even in the setting of mild micronutrient deficiencies.

Methods: In a nested case-control study, we compared maternal iron status at entry to prenatal care (mean gestational age 9.2 +/- 2.6 weeks) between eighty women with healthy vaginal microflora and eighteen women with vaginosis-like microflora. Vaginal microflora status was assessed by assigning a modified Nugent score to a Gram-stained vaginal smear. Maternal iron status was assayed by an array of conventional erythrocyte and serum indicators for iron status assessment, but also by more sensitive and more specific indicators of iron deficiency, including soluble transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron deficiency and the iron deficiency log10[sTfR/ferritin] index as the presently most accurate measure of body storage iron available.

Results: We found no statistically significant correlation between vaginal microflora status and routinely assessed iron parameters. In contrast, a highly significant difference between the healthy and vaginosis-like microflora groups of women was shown in mean values of sTfR concentrations (1.15 +/- 0.30 mg/L versus 1.37 +/- 0.38 mg/L, p = 0.008) and in mean iron deficiency log10[sTfR/ferritin] index values (1.57 +/- 0.30 versus 1.08 +/- 0.56, p = 0.003), indicating a strong association between iron deficiency and vaginosis-like microflora. An sTfR concentration > 1.45 mg/L was associated with a 3-fold increased risk (95%CI: 1.4-6.7) of vaginosis-like microflora and after controlling for maternal age, gestational length, body mass, parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4-14.2).

Conclusion: We conclude that subclinical iron deficiency, presumably resulting from inadequate preconceptional iron supplies, is strongly and independently associated with vaginosis-like microflora during early pregnancy.

Figures

Figure 1

Distribution of sTfR concentrations according to vaginal microflora status. Box-and-whisker plots of the sTfR distributions according to vaginal microflora status during early pregnancy. The thick line represents the median sTfR value, the horizontal box lines the 25th percentile and 75th percentile, and the outer short horizontal lines the boundaries of the sTfR range. Healthy vaginal flora is defined as grade I or lactobacilli-dominated microflora on Gram stain (corresponding to a Nugent score 0 – 3) and disturbed vaginal flora is defined as grade II and grade III flora, this is mixed or gram-negative rods-dominated microflora on Gram stain (corresponding to a Nugent score ≥4).